We propose to continue research in the thieno (2,3-d)pyrimidine nucleoside area by effecting chemical modifications on the 4-amino group and the carbohydrate moiety of 4-amino-5-methyl-1-(beta-d-ribofuranosyl) thieno (2,3-d)pyrimidin-2-one, e.g., 4-amino to 4-mercapto or 4-seleno; ribose yields arabinose. We also propose to synthesize the 5-desmethyl derivative and effect some of the same chemical transformations as well as explore the possibility of electrophilic attack at the C5 position of the nucleoside per se. We also propose to continue our research in the pyridazine nucleoside area which will include the synthesis of the cyclocytidine and ara-c analog and some closely related derivatives. We also propose to finish our proposed research in the area of selenopyrimidine nucleosides and in the 5-diazouracil area which has involved the ring-opening rearrangements without isolation of any bicyclic nucleosides. We also propose a structure activity relationship study based on the antitumor activity observed for 2-methyl-6-ribosyloxozolo (5,4-d) pyrimidin-5-one. We plan to synthesize various bicyclic nucleosides with the pyrimidine moiety being unchanged and replacing the oxazole moiety with other ring systems, e.g., pyrrole, pyrazole, thiazole, benzene, etc. The above will constitute the major areas of proposed research although there is the possibility of additional research being initiated and accomplished which has not been discussed above. The direction of the research will be dictated by the biological and chemotherapeutic activity data received on compounds prepared in this laboratory as well as recent reports of significance in these areas. BIBLIOGRAPHIC REFERENCES: "Ring Contractrons of 5-Diazouracils I. Conversions of 5-Diazouracils into 1,2,3-Triazoles by Hydrolysis and Methanolysis", T.C. Thurber and L.B. Townsend, J. Org. Chem., 41, in press (1976). "Synthesis of Pyridazine Nucleosides Related to the Naturally Occurring Nucleosides Cytidine and Uridine", D.J. Katz, D.S. Wise and L.B. Townsend, J. Heterocyclic Chem., 12, 609 (1975).